title: Challenging single- and multi-probesets gene expression signatures of pathological complete response to neoadjuvant chemotherapy in breast cancer: experience of the REMAGUS 02 phase II trial.
abstract: This study was designed to identify predictive signatures of pathological complete response (pCR) in breast cancer treated by taxane-based regimen, using clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0 devices). The REMAGUS 02 trial (n = 153,training set) and the publicly available M.D. Anderson data set (n = 133, validation set) were used. A re-sampling method was applied. All predictive models were defined using logistic regression and their classification performances were tested through Area Under the Curve (AUC) estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR samples. Single-or 2-probesets signatures, mainly related to ER pathway, were equally predictive of pCR with AUC greater then 0.80. Models including probesets associated with ESR1, MAPT, CA12 or PIGH presented good classification performances. When clinical variables were entered into the model, only CA12 and PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of a few genes provided robust and reliable prediction of pCR.
authors.affiliation: Department of Biostatistics, Curie Institute, Paris 75248, France; Inserm U900, Curie Institute, Paris 75248, France.
authors.forename: F
authors.initials: F
authors.lastname: Valet
authors.forename: P
authors.initials: P
authors.lastname: de Cremoux
authors.forename: F
authors.initials: F
authors.lastname: Spyratos
authors.forename: N
authors.initials: N
authors.lastname: Servant
authors.forename: M E
authors.initials: ME
authors.lastname: Dujaric
authors.forename: D
authors.initials: D
authors.lastname: Gentien
authors.forename: J
authors.initials: J
authors.lastname: Lehmann-Che
authors.forename: V
authors.initials: V
authors.lastname: Scott
authors.forename: B
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: M C
authors.initials: MC
authors.lastname: Mathieu
authors.forename: P
authors.initials: P
authors.lastname: Bertheau
authors.forename: J M
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: J Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: S
authors.initials: S
authors.lastname: Delaloge
authors.forename: S
authors.initials: S
authors.lastname: Giacchetti
authors.forename: E
authors.initials: E
authors.lastname: Brain
authors.forename: O
authors.initials: O
authors.lastname: Tembo
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: B
authors.initials: B
authors.lastname: Asselain
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002256:Carbonic Anhydrases / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012313:RNA / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D043823:Taxoids / Q000008:administration & dosage; D059467:Transcriptome; D016896:Treatment Outcome; D016875:tau Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C054369:MAPT protein, human; D008565:Membrane Proteins; C414442:PIGH protein, human; D011960:Receptors, Estrogen; D043823:Taxoids; D016875:tau Proteins; C080625:taxane; D012313:RNA; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII
keywords: Breast cancer; Neoadjuvant setting; Pathological complete response; Prediction; Transcriptome